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HLA Informatics Group

The HLA Informatics Group, led by Professor Steven GE Marsh, BSc PhD ARCS, Anthony Nolan’s Bioinformatics Director and Deputy Director of Research, has four main areas of interest:

Sequence databases

The HLA Informatics Group designed and now maintains a number of internationally recognised locus specific databases. These include:

The IMGT/HLA Database, which provides a specialist database for sequences of the human major histocompatibility complex (HLA) and includes the official sequences for the World Health Organization Nomenclature Committee For Factors of the HLA System. The IMGT/HLA Database currently contains over 9,900 allele sequences. In addition to the physical sequences, the database holds detailed information about the material the sequence was derived from and data on the validation of the sequences. Further information on the latest HLA Nomenclature can be found at hla.alleles.org.

The IPD-KIR Sequence Database provides a centralised repository for KIR sequences. Killer cell Immunoglobulin-like Receptors (KIRs) have been shown to be highly polymorphic at the allelic and haplotypic level. KIRs are members of the immunoglobulin superfamily (IgSF), formerly called Killer Cell Inhibitory Receptors. They are composed of two or three Ig-domains, a transmembrane region and cytoplasmic tail, which can in turn be short (activatory) or long (inhibitory). The Leukocyte Receptor Complex (LRC) which encodes KIR genes has been shown to be polymorphic, polygenic and complex like the MHC.

The IPD-MHC Sequence Database provides a centralised repository for sequences of the major histocompatibility complex from a number of different species. Through several international collaborations IPD is able to provide the MHC sequences of different species. The sequences provided by each group are curated by experts in the field and then submitted to the central database. Currently the database includes sequence data from domestic dogs, wolves, coyotes, non-human primates, cattle, rats, domestic cats, sheep, fish and pigs.

HSCT donor/patient project

For the past 18 years, the Anthony Nolan Research Institute has coordinated a study to investigate the effects of matching or mismatching a number of different genetic markers on the outcome of haematopoietic stem cell transplants (HSCT) using unrelated donors.

This study involves 37 transplant centres throughout the UK. Over this period we have recruited well over 2,100 volunteer donors and their respective recipients.

We are using the material made available by this project in several studies that have significantly furthered our understanding of the effects of matching HLA at high resolution and in particular the role of the HLA-DPB1 gene.

In addition, we are now beginning to investigate the role of genes other than HLA on transplant outcome, as we believe they may contribute significantly, when taken into consideration with HLA typing.

We are undertaking two projects at this time. The first is trying to establish the effects of NOD2/CARD15 gene polymorphisms on the outcome of unrelated donor HSCTs, while the second is investigating the role of KIR genes.

HLA diversity analysis of the UK population

Anthony Nolan maintains a register of more than 494,000 potential bone marrow donors, each of whom have been typed for some of their HLA genes. This data set represents an ideal source of information for studying the HLA genetic diversity in different UK ethnic groups.

We are undertaking a project to characterise the geographical HLA genetic diversity of the UK population using donors of North European origin. The results of this project aim to improve our recruitment strategies, by identifying regions with higher diversity. This will contribute to creating a more diverse register, and so increase the chances of a patient finding a compatible donor.

This book, written by Steven Marsh, Peter Parham and Linda Barber, presents up-to-date and comprehensive information on the HLA genes. It’s accessible to beginners and experts alike. The book’s focus is the polymorphic HLA genes (HLA-A, B, C, DP, DQ and DR) that are typed in clinical HLA laboratories.

Each gene has a dedicated section in which individual entries describe the structure, functions and population distribution of groups of related allotypes. Fourteen introductory chapters provide a beginners' guide to the basic structure, function, and genetics of the HLA genes, as well as to the nomenclature and methods used for HLA typing.

You can find more information on the HLA FactsBook on the Elseviersite.